Articles producció científica> Bioquímica i Biotecnologia

Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice

  • Datos identificativos

    Identificador: imarina:9242191
    Autores:
    Ettcheto MSánchez-Lopez ECano ACarrasco MHerrera KManzine PREspinosa-Jimenez TBusquets OVerdaguer EOlloquequi JAuladell CFolch JCamins A
    Resumen:
    Background: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg?1 d?1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. © 2021, The Author(s).
  • Otros:

    Autor según el artículo: Ettcheto M; Sánchez-Lopez E; Cano A; Carrasco M; Herrera K; Manzine PR; Espinosa-Jimenez T; Busquets O; Verdaguer E; Olloquequi J; Auladell C; Folch J; Camins A
    Departamento: Bioquímica i Biotecnologia
    Autor/es de la URV: Folch Lopez, Jaume
    Palabras clave: Western blotting Unfolded protein response Synapsis Risk factor Polymerase chain reaction Nonhuman Neuroinflammation Nervous system inflammation Mouse Metabolic alterations Liver Lipid diet Insulin tolerance test In vivo study Hippocampus High fat diet Glucose tolerance test Glucose tolerance Female Dexibuprofen Controlled study Cognitive deficits Chromosome pairing Body weight Article Appswe/ps1de9 Animal model Animal experiment Amyloid plaque Amyloid beta protein Alzheimer´s disease Alzheimer disease Adult ?a plaques
    Resumen: Background: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg?1 d?1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. © 2021, The Author(s).
    Áreas temáticas: Medicina ii General biochemistry,genetics and molecular biology Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: jaume.folch@urv.cat
    Identificador del autor: 0000-0002-5051-8858
    Fecha de alta del registro: 2024-07-27
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-021-00646-w
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Cell And Bioscience. 11 (1):
    Referencia de l'ítem segons les normes APA: Ettcheto M; Sánchez-Lopez E; Cano A; Carrasco M; Herrera K; Manzine PR; Espinosa-Jimenez T; Busquets O; Verdaguer E; Olloquequi J; Auladell C; Folch J (2021). Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice. Cell And Bioscience, 11(1), -. DOI: 10.1186/s13578-021-00646-w
    DOI del artículo: 10.1186/s13578-021-00646-w
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2021
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry & Molecular Biology,Biochemistry, Genetics and Molecular Biology (Miscellaneous)
    Western blotting
    Unfolded protein response
    Synapsis
    Risk factor
    Polymerase chain reaction
    Nonhuman
    Neuroinflammation
    Nervous system inflammation
    Mouse
    Metabolic alterations
    Liver
    Lipid diet
    Insulin tolerance test
    In vivo study
    Hippocampus
    High fat diet
    Glucose tolerance test
    Glucose tolerance
    Female
    Dexibuprofen
    Controlled study
    Cognitive deficits
    Chromosome pairing
    Body weight
    Article
    Appswe/ps1de9
    Animal model
    Animal experiment
    Amyloid plaque
    Amyloid beta protein
    Alzheimer´s disease
    Alzheimer disease
    Adult
    ?a plaques
    Medicina ii
    General biochemistry,genetics and molecular biology
    Biochemistry, genetics and molecular biology (miscellaneous)
    Biochemistry, genetics and molecular biology (all)
    Biochemistry & molecular biology
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